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1.
Calcif Tissue Int ; 109(6): 615-625, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34331548

RESUMO

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder that leads to heterotopic ossification (HO), resulting in progressive restriction of physical function. In this study, low-dose, whole-body computed tomography (WBCT) and dual energy X-ray absorptiometry (DXA) were evaluated to determine the preferred method for assessing total body burden of HO in patients with FOP. This was a non-interventional, two-part natural history study in patients with FOP (NCT02322255; date of registration: December 2014). In Part A (described here), WBCT and DXA scans were individually assessed for HO presence and severity across 15 anatomical regions. All images were independently reviewed by an expert imaging panel. Ten adult patients were enrolled across four sites. The sensitivity to HO presence and severity varied considerably between the two imaging modalities, with WBCT demonstrating HO in more body regions than DXA (76/138 [55%] versus 47/113 [42%]) evaluable regions). Inability to evaluate HO presence, due to overlapping body regions (positional ambiguity), occurred less frequently by WBCT than by DXA (mean number of non-evaluable regions per scan 1.2 [standard deviation: 1.5] versus 2.4 [1.4]). Based on the increased sensitivity and decreased positional ambiguity of low-dose WBCT versus DXA in measuring HO in patients with FOP, low-dose WBCT was chosen as the preferred imaging for measuring HO. Therefore, low-dose WBCT was carried forward to Part B of the natural history study, which evaluated disease progression over 36 months in a larger population of patients with FOP.


Assuntos
Miosite Ossificante , Ossificação Heterotópica , Absorciometria de Fóton , Adulto , Progressão da Doença , Humanos , Miosite Ossificante/diagnóstico por imagem , Ossificação Heterotópica/diagnóstico por imagem , Tomografia Computadorizada por Raios X
2.
Bull Environ Contam Toxicol ; 107(5): 809-813, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34232328

RESUMO

We investigated concentrations of blood total mercury (THg) in three extant populations of endangered Whooping Crane (Grus americana). Blood THg was greater in cranes reintroduced during 2001-2008 that range in the eastern US (median = 0.31 ug/g ww) than both wild cranes in central North America (median = 0.11 ug/g ww) and from captivity (median = 0.01 ug/g ww). The median THg blood concentrations in the two free-ranging populations of Whooping Cranes were low compared to reproductive toxic thresholds suggested for other large bird species (> 4.3 ug/g ww), but a singular elevated concentration was observed in one crane (1.04 ug/g ww; 6% of samples from the reintroduced population). These results likely reflect variable dietary Hg exposure among these populations, but should prompt additional biomonitoring to discern risk of greater Hg exposure nearer to the time of breeding and potential effects on productivity.


Assuntos
Aves , Mercúrio , Animais , América do Norte
3.
FASEB J ; 26(3): 1110-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22125315

RESUMO

A unilateral injection of botulinum toxin A (BTxA) in the calf induces paralysis and profound loss of ipsalateral trabecular bone within days. However, the cellular mechanism underlying acute muscle paralysis-induced bone loss (MPIBL) is poorly understood. We hypothesized that MPIBL arises via rapid and extensive osteoclastogenesis. We performed a series of in vivo experiments to explore this thesis. First, we observed elevated levels of the proosteoclastogenic cytokine receptor activator for nuclear factor-κB ligand (RANKL) within the proximal tibia metaphysis at 7 d after muscle paralysis (+113%, P<0.02). Accordingly, osteoclast numbers were increased 122% compared with the contralateral limb at 5 d after paralysis (P=0.04) and MPIBL was completely blocked by treatment with human recombinant osteoprotegerin (hrOPG). Further, conditional deletion of nuclear factor of activated T-cells c1 (NFATc1), the master regulator of osteoclastogenesis, completely inhibited trabecular bone loss (-2.2±11.9%, P<0.01). All experiments included negative control assessments of contralateral limbs and/or within-animal pre- and postintervention imaging. In summary, transient muscle paralysis induced acute RANKL-mediated osteoclastogenesis resulting in profound local bone resorption. Elucidation of the pathways that initiate osteoclastogenesis after paralysis may identify novel targets to inhibit bone loss and prevent fractures.


Assuntos
Osso e Ossos/metabolismo , Músculo Esquelético/metabolismo , Osteoclastos/metabolismo , Paralisia/metabolismo , Ligante RANK/metabolismo , Animais , Reabsorção Óssea/metabolismo , Reabsorção Óssea/prevenção & controle , Toxinas Botulínicas Tipo A/toxicidade , Contagem de Células , Feminino , Deleção de Genes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/patologia , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/patologia , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Osteoprotegerina/farmacologia , Paralisia/induzido quimicamente , Músculo Quadríceps/metabolismo , Músculo Quadríceps/patologia , Proteínas Recombinantes/farmacologia , Tíbia/metabolismo , Fatores de Tempo
4.
Arch Environ Contam Toxicol ; 65(3): 598-610, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23771631

RESUMO

Mining and smelting in the Southeast Missouri Lead Mining District has caused widespread contamination of soils with lead (Pb) and other metals. Soils from three study sites sampled in the district contained from approximately 1,000-3,200 mg Pb/kg. Analyses of earthworms [33-4,600 mg Pb/kg dry weight (dw)] collected in the district showed likely high Pb exposure of songbirds preying on soil organisms. Mean tissue Pb concentrations in songbirds collected from the contaminated sites were greater (p < 0.05) than those in songbirds from reference sites by factors of 8 in blood, 13 in liver, and 23 in kidney. Ranges of Pb concentrations in livers (mg Pb/kg dw) were as follows: northern cardinal (Cardinalis cardinalis) = 0.11-3.0 (reference) and 1.3-30 (contaminated) and American robin (Turdus migratorius) = 0.43-8.5 (reference) and 7.6-72 (contaminated). Of 34 adult and juvenile songbirds collected from contaminated sites, 11 (32%) had hepatic Pb concentrations that were consistent with adverse physiological effects, 3 (9%) with systemic toxic effects, and 4 (12%) with life-threatening toxic effects. Acid-fast renal intranuclear inclusion bodies, which are indicative of Pb poisoning, were detected in kidneys of two robins that had the greatest renal Pb concentrations (952 and 1,030 mg/kg dw). Mean activity of the enzyme delta-aminolevulinic acid dehydratase (ALAD) in red blood cells, a well-established bioindicator of Pb poisoning in birds, was decreased by 58-82% in songbirds from the mining sites. We conclude that habitats within the mining district with soil Pb concentrations of ≥1,000 mg Pb/kg are contaminated to the extent that they are exposing ground-feeding songbirds to toxic concentrations of Pb.


Assuntos
Exposição Ambiental , Chumbo/toxicidade , Oligoquetos/metabolismo , Poluentes do Solo/toxicidade , Aves Canoras/metabolismo , Animais , Monitoramento Ambiental , Chumbo/análise , Chumbo/sangue , Espectrometria de Massas , Metais Pesados/análise , Metais Pesados/sangue , Metais Pesados/toxicidade , Mineração , Missouri , Poluentes do Solo/análise , Poluentes do Solo/sangue
5.
Arch Environ Contam Toxicol ; 63(4): 586-93, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22864586

RESUMO

We estimated mercury exposure and bioaccumulation in sparrow feathers to determine variation among age groups, between sparrow species, and between feather types. Results of feather mercury studies in piscivorous birds indicate that mercury concentrations tend to increase with age and differ between feather types; however, data for insectivorous birds are lacking. We estimated mercury exposure of two insectivorous and sympatric tidal marsh sparrows: coastal plain swamp sparrow (Melospiza georgiana nigrescens), and seaside sparrow (Ammodramous maritimus). Tidal marshes have favorable conditions for mercury methlyation, thus it is likely that tidal marsh sparrows are exposed to methylmercury. We found no difference in mercury concentrations between males and female birds of both species. Adult swamp sparrow feather mercury concentrations did not differ among adult age groups; therefore, mercury was not found to increase with age in sparrows at the site. Hatch-year birds had significantly greater feather mercury concentrations compared with adult birds for both species. Mercury concentrations in adult seaside sparrows were twice as high as those in adult swamp sparrows suggesting species-specific variation, although concentrations in hatch-year sparrow species did not differ. Mercury concentrations differed between feather types in adults of both species. The first primary feather of both species had at least three times greater mercury concentrations than the outer tail feather possibly reflecting varying depuration rates with feather type.


Assuntos
Monitoramento Ambiental/métodos , Plumas/química , Mercúrio/análise , Pardais/metabolismo , Áreas Alagadas , Asas de Animais/química , Animais , Aves , Poluentes Ambientais/análise , Feminino , Masculino , Compostos de Metilmercúrio/análise , Estações do Ano , Especificidade da Espécie
7.
Ecotoxicol Environ Saf ; 73(6): 1159-64, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20580432

RESUMO

The anticoagulant rodenticide diphacinone was slightly toxic (acute oral LD50 2014 mg/kg) to Northern bobwhite (Colinus virginianus) in a 14-day acute toxicity trial. Precise and sensitive assays of blood clotting (prothrombin time, Russell's Viper venom time, and thrombin clotting time) were adapted for use in quail, and this combination of assays is recommended to measure the effects of anticoagulant rodenticides. A single oral sublethal dose of diphacinone (434 mg/kg body weight) prolonged clotting time at 48 h post-dose compared to controls. At 783 mg/kg (approximate LD02), clotting time was prolonged at both 24 and 48 h post-dose. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and was detected before overt signs of toxicity were apparent at the greatest dosages (2868 and 3666 mg/kg) in the acute toxicity trial. These clotting time assays and toxicity data will assist in the development of a pharmacodynamic model to predict toxicity, and also facilitate rodenticide hazard and risk assessments in avian species.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Colinus , Fenindiona/análogos & derivados , Rodenticidas/toxicidade , Animais , Testes de Coagulação Sanguínea , Colinus/sangue , Colinus/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Dose Letal Mediana , Fenindiona/toxicidade , Medição de Risco , Testes de Toxicidade Aguda
8.
J Clin Psychol ; 66(8): 830-46, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20564683

RESUMO

Identifying psychotherapy processes that likely contribute to client outcome with ethnic minorities is a vital practice and research need, particularly within family-focused, evidence-based treatments (EBT) for youth with externalizing problems. Identifying process variables within a cross-cultural context may improve the efficacy of EBTs by informing psychotherapists how to modify their behavior when working with ethnically diverse clients. The authors described one approach to the development of culturally competent psychotherapy, using an observational coding system comprising Afrocentric codes to investigate culturally relevant therapist behaviors. Qualitative examples illustrated the quantitative findings relating to therapist in-session behavior that promote client engagement and positive responding during a midtreatment session of multisystemic therapy.


Assuntos
Transtorno da Personalidade Antissocial/etnologia , Transtorno da Personalidade Antissocial/reabilitação , Negro ou Afro-Americano/psicologia , Competência Cultural , Terapia Familiar/métodos , Delinquência Juvenil/etnologia , Delinquência Juvenil/reabilitação , Transtornos Relacionados ao Uso de Substâncias/etnologia , Transtornos Relacionados ao Uso de Substâncias/reabilitação , População Branca/psicologia , Adolescente , Terapia Cognitivo-Comportamental , Serviços Comunitários de Saúde Mental , Educação , Prática Clínica Baseada em Evidências , Feminino , Humanos , Masculino , Relações Profissional-Família , Teoria de Sistemas
9.
Environ Monit Assess ; 171(1-4): 671-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20135218

RESUMO

Mercury (Hg) contamination from industrial sources is pervasive throughout North America and is recognized by the US Environmental Protection Agency as a health hazard for wildlife and humans. Avian species are commonly used as bioindicators of Hg because they are sensitive to contaminants in the environment and are relatively easy to sample. However, it is important to select the appropriate avian species to use as a bioindicator, which should be directly related to the project objectives. In this study, we tested the utility of two tidal marsh sparrows, Seaside (Ammodramus maritimus) and Saltmarsh (Ammodramus caudacutus) sparrows, as bioindicator species of the extent of Hg contamination in tidal marshes along the Delaware Bay. To determine the possibility of using one or both of these species, we estimated sparrow blood Hg burden in five Delaware watersheds. We found no difference in Hg concentrations between species (F (1,133) < 0.01, P=0.99), but Saltmarsh Sparrows had limited sample size from each site and were, therefore, not appropriate for a Delaware Bay-wide Hg indicator. Seaside Sparrows, however, were abundant and relatively easy to sample in the five watersheds. Seaside Sparrow blood Hg levels ranged from 0.15 to 2.12 ppm, differed among drainages, and were greatest in two drainages distant from the Delaware Bay shoreline (F (4,95) =2.51, P=0.05). Based on a power analysis for Seaside Sparrow blood Hg, we estimated that 16 samples would be necessary to detect differences among sites. Based on these data, we propose that Seaside Sparrows may be used as a tidal marsh Hg bioindicator species given their habitat specificity, relative abundance, widespread distribution in marsh habitats, ease of sampling, and limited variation in blood Hg estimates within a sampling area. In Delaware Bay, Saltmarsh Sparrows may be too rare (making them difficult to sample) to be a viable tidal marsh Hg bioindicator.


Assuntos
Monitoramento Ambiental , Mercúrio/sangue , Pardais/sangue , Animais , Delaware , Ecossistema , Feminino , Masculino , Água do Mar , Áreas Alagadas
10.
J Appl Physiol (1985) ; 102(5): 1945-52, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17255366

RESUMO

We hypothesized that a 10-s rest interval (at zero load) inserted between each load cycle would increase the osteogenic effects of mechanical loading near previously identified thresholds for strain magnitude and cycle numbers. We tested our hypothesis by subjecting the right tibiae of female C57BL/6J mice (16 wk, n = 70) to exogenous mechanical loading within a peri-threshold physiological range of strain magnitudes and load cycle numbers using a noninvasive murine tibia loading device. Bone responses to mechanical loading were determined via dynamic histomorphometry. More specifically, we contrasted bone formation induced by cyclic vs. rest-inserted loading (10-s rest at zero load inserted between each load cycle) by first varying peak strains (1,000, 1,250, or 1,600 micro epsilon) at fixed cycle numbers (50 cycles/day, 3 days/wk for 3 wk) and then varying cycle numbers (10, 50, or 250 cycles/day) at a fixed strain magnitude (1,250 micro epsilon). Within the range of strain magnitudes tested, the slope of periosteal bone formation rate (p.BFR/BS) with increasing strain magnitudes was significantly increased by rest-inserted compared with cyclical loading. Within the range of load cycles tested, the slope of p.BFR/BS with increasing load cycles of rest-inserted loading was also significantly increased by rest-inserted compared with cyclical loading. In sum, the data of this study indicate that inserting a 10-s rest interval between each load cycle amplifies bone's response to mechanical loading, even within a peri-threshold range of strain magnitudes and cycle numbers.


Assuntos
Adaptação Fisiológica , Osteogênese , Tíbia/fisiologia , Animais , Fenômenos Biomecânicos , Feminino , Modelos Lineares , Camundongos , Camundongos Endogâmicos C57BL , Estresse Mecânico , Suporte de Carga
11.
Bone ; 38(2): 257-64, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16185943

RESUMO

The means by which muscle function modulates bone homeostasis is poorly understood. To begin to address this issue, we have developed a novel murine model of unilateral transient hindlimb muscle paralysis using botulinum toxin A (Botox). Female C57BL/6 mice (16 weeks) received IM injections of either saline or Botox (n = 10 each) in both the quadriceps and calf muscles of the right hindleg. Gait dysfunction was assessed by multi-observer inventory, muscle alterations were determined by wet mass, and bone alterations were assessed by micro-CT imaging at the distal femur, proximal tibia, and tibia mid-diaphysis. Profound degradation of both muscle and bone was observed within 21 days despite significant restoration of weight bearing function by 14 days. The muscle mass of the injected quadriceps and calf muscles was diminished -47.3% and -59.7%, respectively, vs. saline mice (both P < 0.001). The ratio of bone volume to tissue volume (BV/TV) within the distal femoral epiphysis and proximal tibial metaphysis of Botox injected limbs was reduced -43.2% and -54.3%, respectively, while tibia cortical bone volume was reduced -14.6% (all P < 0.001). Comparison of the contralateral non-injected limbs indicated the presence of moderate systemic effects in the model that were most probably associated with diminished activity following muscle paralysis. Taken as a whole, the micro-CT data implied that trabecular and cortical bone loss was primarily achieved by bone resorption. These data confirm the decisive role of neuromuscular function in mediating bone homeostasis and establish a model with unique potential to explore the mechanisms underlying this relation. Given the rapidly expanding use of neuromuscular inhibitors for indications such as pain reduction, these data also raise the critical need to monitor bone loss in these patients.


Assuntos
Toxinas Botulínicas Tipo A/efeitos adversos , Lâmina de Crescimento/fisiologia , Músculo Esquelético/efeitos dos fármacos , Paralisia/induzido quimicamente , Animais , Pesos e Medidas Corporais , Densidade Óssea , Doenças Ósseas Metabólicas , Modelos Animais de Doenças , Epífises/patologia , Feminino , Fêmur/diagnóstico por imagem , Fêmur/patologia , Marcha , Membro Posterior/patologia , Camundongos , Fatores de Tempo , Tomografia Computadorizada por Raios X
12.
Environ Toxicol Chem ; 30(5): 1213-22, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21337606

RESUMO

The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be over 20 times greater in American kestrels (Falco sparverius; median lethal dose 96.8 mg/kg body weight) compared with Northern bobwhite (Colinus virginianus) and mallards (Anas platyrhynchos). Modest evidence of internal bleeding was observed at necropsy, although histological examination of heart, liver, kidney, lung, intestine, and skeletal muscle revealed hemorrhage over a wide range of doses (35.1-675 mg/kg). Residue analysis suggests that the half-life of diphacinone in the liver of kestrels that survived was relatively short, with the majority of the dose cleared within 7 d of exposure. Several precise and sensitive clotting assays (prothrombin time, Russell's viper venom time, thrombin clotting time) were adapted for use in this species, and oral administration of diphacinone at 50 mg/kg increased prothrombin time and Russell's viper venom time at 48 and 96 h postdose compared with controls. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and generally corresponded with the onset of overt signs of toxicity and lethality. In view of the toxicity and risk evaluation data derived from American kestrels, the involvement of diphacinone in some raptor mortality events, and the paucity of threshold effects data following short-term dietary exposure for birds of prey, additional feeding trials with captive raptors are warranted to characterize more fully the risk of secondary poisoning.


Assuntos
Anticoagulantes/toxicidade , Falconiformes/metabolismo , Fenindiona/análogos & derivados , Rodenticidas/toxicidade , Animais , Coagulação Sanguínea/efeitos dos fármacos , Colinus/metabolismo , Relação Dose-Resposta a Droga , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Fenindiona/toxicidade , Baço/efeitos dos fármacos , Baço/patologia , Testes de Toxicidade Aguda
13.
J Fam Psychol ; 23(5): 626-35, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19803599

RESUMO

This study examined whether (a) therapist behaviors thought to enhance family treatment predicted caregiver in-session responses, and (b) caregiver race, racial match between caregiver and therapist, and family financial hardship moderated the relationships between therapist and caregiver behavior. Observers coded caregiver and therapist behavior during one session of multisystemic therapy for substance abusing adolescents. Therapist teaching, focusing on strengths, making reinforcing statements, problem solving, and dealing with practical family needs predicted caregiver engagement and/or positive response, regardless of race, racial match, or financial hardship. Caregiver race, financial hardship, and therapist-caregiver racial match occasionally moderated the relationship between other therapist and caregiver behaviors. Findings suggest both commonalities and differences in how therapist behavior may function to engage caregivers in family treatment, depending on diversity-related factors.


Assuntos
Transtorno da Personalidade Antissocial/etnologia , Transtorno da Personalidade Antissocial/reabilitação , População Negra/psicologia , Cuidadores/psicologia , Terapia Familiar/métodos , Delinquência Juvenil/etnologia , Delinquência Juvenil/reabilitação , Motivação , Relações Profissional-Família , Psicotrópicos , Transtornos Relacionados ao Uso de Substâncias/etnologia , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Teoria de Sistemas , População Branca/psicologia , Adolescente , Adulto , Transtorno da Personalidade Antissocial/psicologia , Criança , Diversidade Cultural , Humanos , Delinquência Juvenil/psicologia , Avaliação de Processos e Resultados em Cuidados de Saúde , Projetos Piloto , Pobreza/etnologia , Pobreza/psicologia , Resolução de Problemas , Ensaios Clínicos Controlados Aleatórios como Assunto , Reforço Verbal , Identificação Social , Transtornos Relacionados ao Uso de Substâncias/psicologia
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